Figure 1.

Mechanisms whereby heparanase, Sulf1, and Sulf2 regulate HS function to promote or inhibit tumor growth and spread. (A) HS modification by these three enzymes can have promoting or inhibiting effects on growth factor (GF) signaling. (B) Heparanase, in association with sheddases, can stimulate HSPG shedding, dispersing autocrine to paracrine signaling. (C) Heparanase and Sulf2 can up-regulate HSPG expression to promote GF signaling. And (D) heparanase can induce exosome secretion allowing tumor cell communication with neighboring cells.